Sensor attachment arrangement for flexible bags

ABSTRACT

An optical sensor holding device adapted to be integrated with a flexible bag, said device comprising
         a bag attachment part made from a material that can be welded to the flexible bag;   a sensor attachment part made from a material to which an optical sensor spot can be attached, wherein the sensor attachment part is forced into an opening in the bag attachment part that is slightly smaller than the sensor attachment part such that the sensor attachment part is kept firmly in place and leakage is minimized.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to an optical sensor holding device.

BACKGROUND OF THE INVENTION

Bioreactors are used in the bioprocess industry for growing cells, e.g.for the purpose of producing biopharmaceuticals. Disposable bioreactorshave been used more and more and are an increasing trend in theindustry. These disposable bioreactors are flexible bags made ofplastic, for example welded polyethylene film. For the culturing ofcells it is important to measure some features of the culture inside thebioreactor. The features could be for example temperature, pH, anddissolved oxygen (DO) etc. In flexible bags it is common to providesensors from the upper side of the bag, like the Cellbag™ 50 L/pH fromGE Healthcare. One disadvantage with this is the risk of the sensor notbeing inside the culture all the time. Optical sensors for measuring forexample pH and DO are provided from for example PreSens. Such an opticalsensor, sometimes called a sensor spot, is a spot of a dye materialtypically comprising two different fluorescent materials. When thesensor spot is illuminated, fluorescent substances of the spot will emitlight. Using suitable fluorescent substances this emitted light can beindicative of a property of the culture, such as pH or DO. Thus thereturned light can be analysed and for example pH or DO can bedetermined. For optimal performance, these sensors should be provided inthe culture all the time. Providing the sensors in the bottom part ofthe bag is often not as convenient as providing the sensor from theupper side due to the support structure often provided under the bag.Furthermore these optical sensors typically can not be attached directlyon the material of the bag due to chemical incompatibility. Anotherissue is that the sensor assembly should be as flat as possible toensure that it always will remain under the liquid surface.

SUMMARY

It is an object of the present invention to provide an optical sensorholding device that solves the problems of prior art described above.

This is achieved in an optical sensor holding device according to claim1.

Suitable embodiments are described in the dependent claims and in thedetailed description below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a is a schematic view of a bioreactor in a rocking supportstructure provided with an optical sensor according to the invention.

FIG. 1 b is an exploded view of the system shown in FIG. 1 a.

FIG. 2 a shows a sensor holding part according to one embodiment of theinvention from one side.

FIG. 2 b shows the sensor holding part of FIG. 2 a from the other side.

FIG. 3 a is a cross section of the sensor attaching arrangementaccording to one embodiment of the invention.

FIG. 3 b is a cross section view of another embodiment of the sensorattaching arrangement before assembling.

FIG. 3 c is a cross section view of the sensor attaching arrangement ofFIG. 3 b when assembled.

FIG. 4 a shows an adaptor part according to one embodiment of theinvention in a non locked position.

FIG. 4 b shows the adaptor part of FIG. 4 a in a locked position.

FIG. 5 a is a closer view of the locking mechanism in one embodiment ofthe invention before locking.

FIG. 5 b is the same view as FIG. 5 a but in locked position, i.e. theadaptor part has been turned to a locked position.

FIG. 6 is a cross section view showing the sensor holding part beinglocked in the adaptor part according to one embodiment of the invention.

FIG. 7 a shows another embodiment of the sensor holding part where thesensor holding part is separated into an inner sensor holding part andan outer sensor holding part.

FIG. 7 b is an exploded view of the inner and outer sensor holding partsof FIG. 7 a.

FIGS. 8 a-8 c shows three different embodiments of adaptor partsaccording to the invention.

FIGS. 9 a and 9 b show schematically a sensor holding part and anadaptor part according to another embodiment of the invention.

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIG. 1 a is a schematic view of a bioreactor 1 in a rocking supportstructure 3. FIG. 1 b shows the same bioreactor system but in anexploded view. In the bottom part of the bioreactor 1 a sensor holdingpart 11 is provided according to the invention. The sensor holding partholds an optical sensor on the inside of the bag. Details of this willbe described further down in the description. An optical fibre 7 isprovided to a position close to the position of the optical sensor butoutside the bag with the help of an adaptor part 41 (described in detailbelow). A monitor 9 is also shown where the readings from the opticalsensor can be monitored.

According to the invention a sensor holding part (also called an opticalsensor holding device) is provided inside the bag. The sensor holdingpart is integrated with the bag by means of for example welding. Anadaptor part holding the optical fibre is provided outside the bag. Thesensor holding part comprises an optical sensor and first locking partsprotruding out from the bag. These first locking parts are adapted tomate with second locking parts of the adaptor part such that the opticalfibre in the adaptor part will be safely positioned to and cancommunicate with the sensor inside the bag. Suitably the locking partsprovide a locking mechanism that holds the optical fibre in a stableposition in relation to the sensor in all directions. Suitably theoptical fibre is provided lying flat along the bottom of the bag, i.e.the optical fibre is not pointing towards the sensor in the bag. Insteada mirror is provided in the adaptor part such that the light can bedirected to the sensor when the adaptor part is positioned below thesensor. This is suitable because the support structure does not need tobe adapted to the sensor attachment arrangement. Hereby this sensorattachment arrangement can be used on already existing systems withoutany adaptation. Furthermore, since no part of the sensor attachmentarrangement is secured to the support structure, the bag can be freelymoved together with the sensor and the sensor attachment arrangement.More description around the details of suitable embodiments of theinvention is given below.

FIG. 2 a is a view of a sensor holding part 11 (also called an opticalsensor holding device 11) according to one embodiment of the invention.The sensor holding part 11 is in one embodiment positioned inside thebag and secured to the inner bag surface for example by means ofwelding. In another embodiment the sensor holding part is welded to theoutside of the bag surface and a hole is provided in the bag surfacearound the sensor. In FIG. 2 a the side adapted to face the interior ofthe bag is shown. In this embodiment the sensor holding part 11 iscircular. This is suitable because a circular shape will give rise toless tension in the joint between the bag and the sensor holding partthan would a shape with sharp edges. Furthermore, tension stress cancause creeping deformation of the sensor holding part. The circulargeometry also reduces the risk for dimension changes due to differentshrinkage in the molding process. However other geometries of the sensorholding part would also be possible. In the centre of the sensor holdingpart 11 the optical sensor 13, is provided. The optical sensor is a dyeas described in the background chapter and can also be called a sensorspot. The sensor holding part should be provided in a material that canbe welded to the bag material. The bag is often made from polyethyleneand in this embodiment also the sensor holding part is made frompolyethylene. However, the material of the sensor 13 can not be attacheddirectly to polyethylene and therefore the sensor has been provided on asmall piece of another material to which the sensor can be attached andwhich is transparent. In this embodiment polycarbonate has been used.This is described in more detail below in relation to FIG. 3.

FIG. 2 b shows the sensor holding part 11 of FIG. 2 a from the otherside, i.e. from the side pointing out from the bag. In this embodimentfour first locking means in the form of hooks 17 a, 17 b, 17 c, 17 d areprovided protruding out from the sensor holding part. The hooks areprovided on the circumference of a circle. The number of the hooks canalso be 2, 3, 5 or even more. The first locking means 17 a, b, c, d areadapted to protrude out from the bag when the sensor holding part ispositioned inside the bag. At least one hole needs to be provided in thebag surface to let the first locking means 17 a, b, c, d through. In oneembodiment a circular hole 23 as large as comprising all the firstlocking means 17 a, b, c, d is provided in the bag. The sensor holdingpart is welded to the bag in order to prevent any leakage. In anotherembodiment the same circular hole is provided in the bag and furthermorea smaller circular piece of bag film is welded over the central part ofthe sensor holding part but inside the first locking means 17 a, b, c,d. This smaller circular piece of bag film will hereby cover the sensorin the middle of the sensor holding part. This could be suitable ifthere is any risk of leakage through the sensor attaching arrangement.This is described in more detail below in relation to FIG. 3. In anotherembodiment it would also be possible to provide one separate hole in thebag for each first locking means, i.e. in this embodiment four holeswould be provided. The sensor holding part needs then to be welded tothe bag around all these four holes in order to prevent any leakage.Alternatively, the bag surface could be welded to the sensor holdingpart in one circle on the inside of the locking means and one circleoutside the locking means.

FIG. 3 a is a cross section of a central part of the sensor attachmentarrangement according to one embodiment of the invention. According tothe invention the sensor holding part 11 (also called the optical sensorholding device 11) comprises two parts. One bag attachment part 31adapted to be welded to the bag and one sensor attachment part 33 wherethe sensor 13 is provided. The sensor attachment part 33 is made of amaterial to which the sensor 13 can be attached. This could be forexample polycarbonate. The sensor attachment part 33 is pressed fit intoan opening 34 in the bag attachment part 31. The bag attachment part 31is made from a material that can be welded to the bag. Many bags aremade from polyethylene and in this example also the bag attachment part31 is made from polyethylene. The reason why the sensor 13 is notattached directly to the bag attachment part 31 is that the sensor 13used in this example can not be attached to a material that also can bewelded to the bag. The bag is made from polyethylene and therefore asuitable material for the sensor holding part is polyethylene. Howeverthe material of the sensor 13 used in this example can not be attachedto polyethylene. The press fit of the sensor attachment part 33 in theopening 34 in the bag attachment part 31 disclosed here in relation toFIG. 3 a is a way to solve this problem. The sensor attachment part 33should be slightly bigger than the opening 34. Furthermore the sensorattachment part 33 is provided with a chamfer 35. This will give aradial pressure on the sensor attachment part 33 for the purpose ofpreventing leakage through the free press fit. This minimizes the riskof getting any liquid or dirt in the opening 37 below the sensorattachment part 33 where light will pass during the optical reading.

Furthermore, a locking shoulder 38 is provided in the opening 34 in thebag attachment part 31. The locking shoulder 38 should keep the sensorattachment part 33 in place after having been forced to pass saidlocking shoulder 38 when pressed fitted into the opening 34.

In this embodiment a circular piece of bag film 21 is also provided.This piece of bag film 21 is welded to the bag attachment part 31 aroundthe central part of the bag attachment part 31 where the sensor 13 isprovided. The purpose is to prevent any possible leakage outside the bagif such a leakage would occur through the press fit. However, if thepress fit really is leakage free and reliable this circular piece of bagfilm 21 would not be necessary.

In FIG. 3 a an adaptor part 41 is also shown attached to the sensorholding part 11. An optical fibre 7 is positioned into the adaptor part41. A combined mirror and lens 39 is provided in the adaptor part 41connected to the optical fibre 7. When the sensor holding part 11 andthe adaptor part 41 are connected the combined mirror and lens 39 isprovided right beneath the sensor in the sensor holding part 11. Thecombined mirror and lens 39 directs and focuses the light from theoptical fibre 7 onto the sensor spot 13. The sensor 13 is herebyilluminated via the fibre 7 and the excited fluorescent sensor 13 emitslight that is monitored via the fibre 7. The light paths are shown byarrows. With this arrangement the optical fibre is provided along thesurface of the bottom part of the bag and the support structure needsnot to be adapted in any way. The first and second locking parts keepingthe sensor holding part and the adaptor part together will be furtherdescribed below.

FIG. 3 b is a cross section view of a central part of the sensorattachment arrangement according to another embodiment of the inventionbefore assembly. FIG. 3 c is a cross section of the embodiment shown inFIG. 3 b after assembly. According to the invention a sensor holdingpart 11′ (also called an optical sensor holding device 11′) comprisestwo parts. One bag attachment part 31′ adapted to be welded to the bagand one sensor attachment part 33′ where the sensor 13 is provided. Thesensor attachment part 33′ is made of a material to which the sensor 13can be attached. This could be for example polycarbonate. The sensorattachment part 33′ is pressed fit into an opening 34′ in the bagattachment part 31′. The bag attachment part 31′ is made from a materialthat can be welded to the bag. Many bags are made from polyethylene andin this example also the bag attachment part 31′ is made frompolyethylene. The reason why the sensor 13 is not attached directly tothe bag attachment part 31′ is that the sensor 13 used in this examplecan not be attached to a material that also can be welded to the bag.The bag is made from polyethylene and therefore a suitable material forthe sensor holding part is polyethylene. However the material of thesensor 13 used in this example can not be attached to polyethylene. Thepress fit of the sensor attachment part 33′ in the opening 34′ in thebag attachment part 31′ disclosed here in relation to FIGS. 3 b and 3 cis a way to solve this problem. The sensor attachment part 33′ should beslightly bigger than the opening 34′. In this embodiment described inFIGS. 3 b and 3 c suitably a force is applied around the opening 34′combined with a holding device 40 on the opposite side as shown by theforce arrows in FIG. 3 b when the sensor attachment part 33′ should bepressed into the bag attachment part 31′. Hereby the entrance into theopening 34′ will get larger (see also deformation arrows) and it will beeasier to insert the sensor attachment part 33′. When the sensorattachment part 33′ is in place the force will be released and thesensor attachment part 33′ will be positioned stably in the opening 34′.Furthermore the sensor attachment part 33′ is provided with a chamfer35′. This will give a radial pressure on the sensor attachment part 33′for the purpose of preventing leakage through the free press fit.

Furthermore, a hook 36 is provided on the sensor attachment part 33′which hook 36 will be pressed into the walls of the opening 34′ of thebag attachment part 31′ after insertion and assure a stable position ofthe sensor attachment part 33′ in the bag attachment part 31′.

FIG. 3 c is a cross section view of the sensor attaching arrangement ofFIG. 3 b when assembled. In FIG. 3 c an adaptor part 41 is also shownattached to the sensor holding part 11′. An optical fibre 7 ispositioned into the adaptor part 41. A combined mirror and lens 39 isprovided in the adaptor part 41 connected to the optical fibre 7. Whenthe sensor holding part 11′ and the adaptor part 41 are connected thecombined mirror and lens 39 is provided right beneath the sensor in thesensor holding part 11′. The combined mirror and lens 39 directs andfocuses the light from the optical fibre 7 onto the sensor spot 13. Thesensor 13 is hereby illuminated via the fibre 7 and the excitedfluorescent sensor 13 emits light that is monitored via the fibre 7. Thelight paths are shown by arrows. With this arrangement the optical fibreis provided along the surface of the bottom part of the bag and thesupport structure needs not to be adapted in any way. The first andsecond locking parts keeping the sensor holding part and the adaptorpart together will be further described below. In this embodiment acircular piece of bag film 21 is also provided. This piece of bag film21 is welded to the bag attachment part 31′ around the central part ofthe bag attachment part 31′ where the sensor 13 is provided. The purposeis to prevent any possible leakage outside the bag if such a leakagewould occur through the press fit. However, if the press fit really isleakage free and reliable this circular piece of bag film 21 would notbe necessary.

FIG. 4 a shows an adaptor part 41 according to one embodiment of theinvention. Suitably the adaptor part is provided in a material that isstiffer than the material of the sensor holding part 11. One example ofa suitable material for the adaptor part is POM (Polyacetal plastic orDelrin plastic) or Peek (polyetereterketone plastic). In FIG. 4 a it isshown how the first locking means 17 a, b, c, d of the sensor holdingpart 11 are fitted into second locking means 43 a, b, c, d, in theadaptor part 41 in a non locked position. However, the rest of thesensor holding part 11 is not shown in order to make it clearer. Thesecond locking means 43 a, b, c, d are in this embodiment provided asfour tracks on the circumference of a circle. The dimensions are adaptedfor receiving the first locking means 17 a, b, c, d of the sensorholding part 11. In this embodiment each track 43 a, b, c, d comprisesguiding surfaces leading the hooks into a locking position, i.e. afterhaving rotated the adaptor part 41 in relation to the sensor holdingpart 11 (as shown in FIG. 4 b) the first locking means 17 a, b, c, dhave been guided into a second position within the tracks which is alocked position. These details are described in relation to FIGS. 5 aand 5 b.

FIG. 4 b shows the adaptor part of FIG. 4 a in a locked position.

FIG. 5 a is a closer view of the locking mechanism in one embodiment ofthe invention before locking. One first locking means 17 a in the formof a hook is shown inserted into one second locking means 43 a in theform of a track. A radial guiding surface 44 on the inner surface of thetrack 43 a is provided for guiding a corresponding hook guiding surface46 on the hook 17 a into a radial locked position. Possibly the hook 17a is also pressed somewhat outwardly by the guiding surface 44.Furthermore a locking bump 45 is shown in the track 43 a. A grippingpart 48 of the hook 17 a will be caught by an inclined surface 42 of thetrack leading up to the locking bump 45 and the hook 17 a will pass overthe locking bump 45 when the adaptor part 41 is rotated in relation tothe sensor holding part 11. The purpose of the locking bump 45 is toprevent the hook 17 a from rotating back.

FIG. 5 b is the same view as FIG. 5 a but in locked position, i.e. theadaptor part has been rotated to a locked position. Because all fourlocking parts provided in a circle are locked and because the lockingmechanism is securing the adaptor part 41 in relation to the sensorholding part 11 in all directions the combined mirror and lens 39 of theadaptor part 41 can be kept steadily in relation to the sensor 13.Furthermore, this locking mechanism provides a very low tension stresson the sensor holding part. This is important because the sensor holdingpart is made from polyethylene and this material tends to be subjectedto creepings/relaxation. Hereby the risk for creeping/relaxation in thesensor holding part is reduced to a minimum by the locking mechanismdescribed here.

FIG. 6 is a cross section view showing the sensor holding part 11 beinglocked in the adaptor part 41 according to one embodiment of theinvention. In this view a contact surface 49 between the sensor holdingpart (possibly through the piece of bag film 21) and the adaptor part 41can be seen. When the gripping part 48 of the hook 17 is pressed by thetrack 43 into the locked position the sensor holding part and theadaptor part will come into contact at contact surface 49 (possiblythrough the piece of bag film 21). This contact is important because thedistance between the sensor and the combined mirror and lens need to bekept constant and contact surfaces pressed towards each other. This willwork well if the tension stress is kept at a minimum level and thereforereduces the risk for creeping of the sensor part.

FIG. 7 a shows another embodiment of a sensor holding part 51 where thesensor holding part is separated into an inner sensor holding part 53and an outer locking part 55. FIG. 7 b is an exploded view of the sensorholding part of FIG. 7 a. In this embodiment the bag 65 needs not to bepenetrated by the first locking means. The bioreactor bag surface can bekept intact. This could be good for preventing any contamination riskfor the cell growth process. First locking means 57 are provided on theouter locking part 55. The inner sensor holding part 53 is welded to thebag surface and it comprises the sensor 59 in the middle facing theinterior of the bag. The sensor attachment arrangement is suitably thesame as described in relation to FIG. 3. The outer sensor holding part55 is welded to the outside of the bag. The inner sensor holding part 53and the outer locking part 55 will be welded together by bending the bag65 according to FIG. 7 a and then an inner bag support ring 61 and anouter bag support ring 63 will be welded on top and on the bottom andsecure the assembly. The adaptor part is suitably the same as describedin relation to FIGS. 4 a and 4 b.

FIGS. 8 a-8 d shows four different embodiments of adaptor partsaccording to the invention. Of course both the first and second lockingmeans of the invention can be designed in different forms. The resultthat should be achieved is a locking position where the two parts arekept together and are locked together in all directions. Furthermore thegeometry of the locking is important such that any creeping in thesensor holding part can be prevented. Four alternative embodiments ofthe adaptor part are shown in FIGS. 8 a-8 d where FIG. 8 a shows theadaptor part already described in relation to FIGS. 4 and 5. In thisembodiment the locking is made in axial direction. The embodiments shownin FIGS. 8 b, 8 c and 8 d provide a locking in radial direction.

The sensors described above are optical sensors. These could be forexample sensors for pH, DO, carbondioxide (CO₂), biomass, UV detectionand IR detection.

FIGS. 9 a and 9 b show schematically another embodiment of the inventionwhere the first and second locking parts are designed differently. Asensor holding part 91 is shown having four first locking means 93 a, b,c, d in the form of plugs with larger heads 95 a, b, c, d. An adaptorpart 97 is also shown having four second locking means 99 a, b, c, d inthe form of receiving holes. In FIG. 9 b one of the second locking means99 a is shown in cross section. The second locking means 99 a comprisesa retaining means 101 a in the form of a section in the receiving holehaving a smaller diameter than the rest of the hole and edges adaptedfor letting the larger head 95 a of the first locking means 93 a passthrough the retaining means 101 a when a force is applied from above.The edges of the retaining means 101 are further adapted for retainingthe head 95 a below the retaining means 101 when it has been presseddown there. A sensor is provided in the middle of the sensor holdingpart in the same way as described in for example relation to FIGS. 2 aand b and an optical fibre is provided in the adaptor part in the sameway as described in relation to FIG. 3. There are of course many otherpossible ways of designing the first and second locking means.

One important benefit with the invention is that a support structureprovided under the flexible bag need not be adapted in any way to thesensor attachment arrangement. The bag can be freely moved together withthe sensor attachment arrangement and be used in any system. Anotherfeature of the sensor attachment arrangement is that it is very flat andof low height. This is advantageous since it is important that itseffect on the mixing of the culture in the bioreactor bag by protrudinginto the bag is limited. At the same time also small volumes of culturein the bag will cover the sensor. The different locking mechanismsdescribed above and the mirror provided in the adaptor part are bothimportant components in making the sensor attachment arrangement as flatas possible.

1. An optical sensor holding device (11; 11′) adapted to be integratedwith a flexible bag (1), said device comprising a bag attachment part(31; 31′) made from a material that can be welded to the flexible bag(1); a sensor attachment part (33; 33′) made from a material to which anoptical sensor spot (13) can be attached, wherein the sensor attachmentpart (33; 33′) is forced into an opening (34; 34′) in the bag attachmentpart (31; 31′) that is slightly smaller than the sensor attachment part(33; 33′) such that the sensor attachment part is kept firmly in placeand leakage is minimized.
 2. The optical sensor holding device of claim1, wherein said sensor attachment part (33; 33′) is adapted to providethe optical sensor inside the flexible bag in direct communication witha culture liquid inside the bag.
 3. The optical sensor holding device ofclaim 1, wherein the bag attachment part (31; 31′) is made frompolyethylene and the sensor attachment part (33; 33′) is made frompolycarbonate.
 4. The optical sensor holding device of claim 1, whereinthe sensor attachment part (33; 33′) is provided with a chamfer (35;35′) whereby this will give a radial pressure on the sensor attachmentpart (33; 33′) for the purpose of preventing leakage through the freepress fit.
 5. The optical sensor holding device of claim 1, wherein alocking shoulder (38) is provided in the opening (34) in the bagattachment part (31) whereby the locking shoulder (38) should keep thesensor attachment part (33) in place after having been forced to passsaid locking shoulder (38) when pressed fitted into the opening (34). 6.The optical sensor holding device of claim 1, wherein the sensor holdingdevice (11; 11′) is integrated with the flexible bag in the bottom ofthe bag.
 7. The optical sensor holding device of claim 1, wherein theflexible bag (1) is a bioreactor provided on a support structure (3).